The primary goal of this revised application (MH64173), which is ancillary to the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), is to reliably capture the concentration exposure of the antipsychotics (risperidone, olanzapine, ziprasidone, fluphenazine, perphenazine, and clozapine) using mixed effect population pharmacokinetic methodologies. The population pharmacokinetic approach is ideally suited for analyzing drug concentration data from large clinical intervention trials because patient-specific as well as overall population pharmacokinetic parameters can be determined using only a few plasma samples per patient. An understanding of pharmacokinetic variability is essential to rational drug prescribing. The population pharmacokinetic approach will permit determination of the extent of variability in drug exposure associated with the use of atypical antipsychotics in large populations under conditions that mirror clinical practice. In addition, the ability of population pharmacokinetic models to capture subjects' drug exposure utilizing single concentration measurements will be assessed in this study. Population pharmacokinetics has also been successfully used to identify sources of variability in drug concentration exposure. Therefore, this ancillary study will provide an innovative way to make optimal use of plasma samples that are being obtained in the CATIE trials. The CATIE trials will recruit up to 2,250 patients providing from 1 to 6 plasma concentration samples per subject for each medication. A separate population pharmacokinetic model will be constructed for each drug incorporating covariate effects. Specific covariates will be then be evaluated as potential contributors to drug exposure variability. Demographic covariates to be examined are age, sex, race/minority status, and body mass index. The potential impact of additional covariates such as prior medication exposure, concomitant medications, smoking status, estimated renal clearance, and treatment adherence will also be assessed. By providing pharmacokinetic data on the atypical antipsychotics under "real world" conditions, this study has broad public health implications, leading to greater awareness of the need to individualize antipsychotics pharmacotherapy for patients suffering from either schizophrenia or Alzheimer's disease.